TY - JOUR
T1 - A Widespread Radical-Mediated Glycolysis Pathway
AU - Ma, Kailiang
AU - Xue, Bo
AU - Chu, Ruoxing
AU - Zheng, Yuchun
AU - Sharma, Shishir
AU - Jiang, Li
AU - Hu, Min
AU - Xie, Yiren
AU - Hu, Yiling
AU - Tao, Tiantian
AU - Zhou, Yan
AU - Liu, Dazhi
AU - Li, Zhi
AU - Yang, Qiaoyu
AU - Chen, Yiwei
AU - Wu, Songgu
AU - Tong, Yang
AU - Robinson, Robert C.
AU - Yew, Wen Shan
AU - Jin, Xinghua
AU - Liu, Yanhong
AU - Zhao, Huimin
AU - Ang, Ee Lui
AU - Wei, Yifeng
AU - Zhang, Yan
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/9/25
Y1 - 2024/9/25
N2 - Glycyl radical enzymes (GREs) catalyze mechanistically diverse radical-mediated reactions, playing important roles in the metabolism of anaerobic bacteria. The model bacterium Escherichia coli MG1655 contains two GREs of unknown function, YbiW and PflD, which are widespread among human intestinal bacteria. Here, we report that YbiW and PflD catalyze ring-opening C-O cleavage of 1,5-anhydroglucitol-6-phosphate (AG6P) and 1,5-anhydromannitol-6-phosphate (AM6P), respectively. The product of both enzymes, 1-deoxy-fructose-6-phosphate (DF6P), is then cleaved by the aldolases FsaA or FsaB to form glyceraldehyde-3-phosphate (G3P) and hydroxyacetone (HA), which are then reduced by the NADH-dependent dehydrogenase GldA to form 1,2-propanediol (1,2-PDO). Crystal structures of YbiW and PflD in complex with their substrates provided insights into the mechanism of radical-mediated C-O cleavage. This “anhydroglycolysis” pathway enables anaerobic growth of E. coli on 1,5-anhydroglucitol (AG) and 1,5-anhydromannitol (AM), and we probe the feasibility of harnessing this pathway for the production of 1,2-PDO, a highly demanded chiral chemical feedstock, from inexpensive starch. Discovery of the anhydroglycolysis pathway expands the known catalytic repertoire of GREs, clarifies the hitherto unknown physiological functions of the well-studied enzymes FsaA, FsaB, and GldA, and demonstrates how enzyme discovery efforts can cast light on prevalent yet overlooked metabolites in the microbiome.
AB - Glycyl radical enzymes (GREs) catalyze mechanistically diverse radical-mediated reactions, playing important roles in the metabolism of anaerobic bacteria. The model bacterium Escherichia coli MG1655 contains two GREs of unknown function, YbiW and PflD, which are widespread among human intestinal bacteria. Here, we report that YbiW and PflD catalyze ring-opening C-O cleavage of 1,5-anhydroglucitol-6-phosphate (AG6P) and 1,5-anhydromannitol-6-phosphate (AM6P), respectively. The product of both enzymes, 1-deoxy-fructose-6-phosphate (DF6P), is then cleaved by the aldolases FsaA or FsaB to form glyceraldehyde-3-phosphate (G3P) and hydroxyacetone (HA), which are then reduced by the NADH-dependent dehydrogenase GldA to form 1,2-propanediol (1,2-PDO). Crystal structures of YbiW and PflD in complex with their substrates provided insights into the mechanism of radical-mediated C-O cleavage. This “anhydroglycolysis” pathway enables anaerobic growth of E. coli on 1,5-anhydroglucitol (AG) and 1,5-anhydromannitol (AM), and we probe the feasibility of harnessing this pathway for the production of 1,2-PDO, a highly demanded chiral chemical feedstock, from inexpensive starch. Discovery of the anhydroglycolysis pathway expands the known catalytic repertoire of GREs, clarifies the hitherto unknown physiological functions of the well-studied enzymes FsaA, FsaB, and GldA, and demonstrates how enzyme discovery efforts can cast light on prevalent yet overlooked metabolites in the microbiome.
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U2 - 10.1021/jacs.4c07718
DO - 10.1021/jacs.4c07718
M3 - Article
C2 - 39283600
AN - SCOPUS:85204172369
SN - 0002-7863
VL - 146
SP - 26187
EP - 26197
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 38
ER -